Valsartan, chemically (S)—N-(1-carboxy-2-methyl-prop-1-yl)-N-pentanoyl-N-[2′-(1H-tetrazol-5-yl)-biphenyl-4-yl-methyl]-amine of formula (II),

is an angiotensin receptor antagonist. It is marketed under the trade name Diovan® to treat high blood pressure, congestive heart failure and to reduce death of people with left ventricular dysfunction after having a heart attack. It is also used in combination with other pharmaceutically active compounds. Valsartan is present in Diovan® in its free acid form. WO2002006253 discloses several salts of valsartan. Examples 5 and 11 describe processes to prepare valsartan disodium.
Sacubitril, chemically (2R,4S)-5-biphenyl-4-yl-5-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester of formula (I),

is a neutral endopeptidase inhibitor which is used in combination with valsartan.
Sacubitril is a prodrug that is activated by hydrolysis of the ester functionality. Several salts of sacubitril have been described in literature. Sacubitril sodium is disclosed in EP0555175. The process to prepare the sodium salt is described in example 1 of this application. Several polymorphic forms of sacubitril sodium are disclosed in CN105837464.
The combination drug sacubitril/valsartan is marketed by Novartis under the brand name Entresto® to treat heart failure. The fixed-dose combination product contains a co-crystal complex of the sodium salts of the two individual compounds in hydrated form. Entresto® is supplied for oral administration as immediate release film-coated tablets in three strengths: 24/26, 49/51 and 97/103 mg, containing respectively 24.3 mg sacubitril/25.7 mg valsartan, 48.6 mg sacubitril/51.4 mg valsartan and 97.2 mg sacubitril/102.8 mg valsartan. According to the information published by the EMA in the European Public Assessment Report (EPAR), the co-crystal form identified by Novartis renders valsartan more bioavailable than in its standalone formulations.
Entresto® is a BCS class IV product, having low permeability and low solubility. The drug substance is practically insoluble in water.
WO2007056546 discloses the trisodium hemipentahydrate supramolecular complex, as present in Entresto® and WO2009061713 discloses solid oral dosage forms thereof.
WO2017012600 discloses pharmaceutical compositions containing valsartan free acid, or a pharmaceutically acceptable salt thereof, sacubitril free acid, or a pharmaceutically acceptable salt thereof, and suitable excipients. In the application, several tablet compositions comprising different combinations of sacubitril free acid, its sodium, calcium or cyclohexylammonium salt with valsartan free acid, its sodium or disodium salt are described. The total amount of impurities in the compositions after storage under different conditions is given. No information regarding dissolution behavior or comparison with Entresto® tablets is made.
It would be advantageous to develop a pharmaceutical composition comprising a physical mixture of sacubitril sodium and valsartan disodium which would be bioequivalent to Entresto®. This composition should exhibit excellent long term stability and should be suitable for production on commercial scale by applying techniques and equipment commonly used in industry.